Phosphaturic effect of L-NMMA in the presence of parathyroid hormone

Marcine J. Onsgard-Meyer, Ryan J. Kerrigan, Michelle Collins, Ali A. Khraibi, Franklyn G. Knox

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Abstract

The objective of this study was to examine the effect of N(G)- monomethyl-L-arginine (L-NMMA) on phosphate excretion in the presence and absence of parathyroid hormone (PTH). Renal clearances were obtained before and during infusion of L-NMMA (15 mg/kg bolus and 500 μg·kg-1·min-1 infusion) in Sprague-Dawley rats with intact parathyroid glands (n = 6), in thyroparathyroidectomized (TPTX) rats receiving a constant infusion of PTH- (1-34) (0.01-0.03 U·kg-1·min-1) (n = 11) throughout the experiment, or in TPTX rats that received an acute infusion of PTH-(1-34) (33 U/kg bolus and 1 U·kg-1·min1-1 infusion) after L-NMMA infusion alone (n = 7). In rats with intact parathyroid glands, L-NMMA increased the fractional excretions of phosphate (FE(Pi)) and sodium (FE(Na)) and mean arterial pressure (MAP) (Δ8.6 ± 1.5%, Δ0.62 ± 0.1%, and Δ26.7 ± 4.9 mmHg, respectively; P < 0.05). In TPTX rats receiving a constant infusion of PTH, L-NMMA again increased FE(Pi), FE(Na), and MAP (Δ9.5 ± 3.6%, Δ1.1 ± 0.4%, and Δ28.4 ± 4.5 mmHg, respectively; P < 0.05). However, in TPTX rats, L-NMMA alone did not increase FE(Pi) (Δ0.9 ± 0.3%), whereas the subsequent infusion of PTH with L-NMMA increased FE(Pi) (Δ15.6 ± 3.1%; P < 0.05). In an additional group of intact and TPTX rats, the fractional excretion of lithium (FE(Li)) was measured as an index of proximal reabsorption. L-NMMA increased FE(Li) in intact rats (Δ13.2 ± 2.6%; P < 0.05), but not in TPTX rats (Δ4.2 ± 3.3%). In conclusion, L-NMMA increases phosphate excretion in association with increases in MAP and FE(Na), and this phosphaturic effect is dependent on the presence of PTH.

Original languageBritish English
Pages (from-to)R1477-R1480
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume271
Issue number6 40-6
DOIs
StatePublished - Dec 1996

Keywords

  • kidney
  • nitric oxide
  • phosphate excretion
  • pressure natriuresis
  • proximal tubule
  • Sprague-Dawley rat
  • thyroparathyroidectomy

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